LH

The LH test provides fundamental information for the evaluation of reproductive functions by measuring the level of luteinizing hormone. An increase or decrease in this hormone offers important clinical clues in the diagnosis of ovulation status, hormonal imbalances and gonadal dysfunction.

Analysis of LH levels plays a critical role in determining the timing of ovulation. The sudden rise of LH within the cycle indicates that ovulation is approaching and supports accurate timing in fertility evaluations.

LH screening is also used to assess gonadal dysfunction in men. Changes in hormone levels provide information about testosterone production and the functioning of the pituitary–gonadal axis, thereby guiding the diagnostic process.

Serial LH measurements are important in the follow-up of hormonal disorders such as polycystic ovary syndrome. Regular evaluation facilitates analysis of the LH/FSH ratio and contributes to the planning of long-term hormonal management strategies.

What Is LH?

LH (Luteinizing Hormone) is a hormone secreted by the pituitary gland that plays an important role in the regulation of the reproductive system. In women, it triggers ovulation, while in men it stimulates testosterone production. LH levels are used in the evaluation of infertility, menstrual irregularities, polycystic ovary syndrome (PCOS) and pituitary function. It is measured with a blood test and helps in understanding the hormonal balance.

What is the main role of LH in egg production?

To understand the role of LH in the ovary, imagine a “two-cell factory” working in perfect cooperation. There are two neighboring layers of cells surrounding the egg (called theca and granulosa cells), and for this factory to work at full capacity, both LH and another important hormone called FSH (Follicle Stimulating Hormone) are needed.

The system works as follows: LH binds to theca cells in the outer layer of the ovary and gives them the signal to “start production.” This signal enables these cells to use cholesterol to produce androgens, a type of “male hormone” that acts as raw material. This raw material then passes to the neighboring layer of cells (granulosa cells). At this point, FSH comes into play. FSH gives these second-layer cells the command: “Take this raw material (androgens) and convert it into estrogen, the ‘female hormone’ (the final product)!”

This cooperation is vital. Because the first cells cannot produce estrogen, and the second cells cannot produce the raw material (androgen) from scratch. The high estrogen levels required for healthy egg development are only possible through the flawless harmony of these two cell types and the two hormones (LH and FSH).

In IVF treatment, our goal is to grow many eggs, and this requires much more estrogen production than normal. If LH is suppressed more than necessary during a treatment protocol, this factory suffers from “raw material” scarcity. No matter how high the FSH dose is, estrogen production remains insufficient. This may negatively affect egg development and quality. Therefore, keeping LH at an “adequate” level during treatment is a critical balance.

Does the LH hormone only trigger ovulation?

In general, LH is thought of only as the “final touch” hormone that triggers ovulation. However, scientific evidence shows that LH is also involved in much earlier stages of the egg’s months-long development journey.

LH helps even the smallest “sleeping” egg precursors (primordial follicles) to wake up and begin their growth journey. If a woman has chronic LH deficiency (for example, in certain hormonal conditions such as hypogonadotropic hypogonadism), development of these smallest eggs may slow down or stop. This can reduce the pool of “antral follicles” that are ready at the beginning of the cycle to respond to treatment.

This also changes the way we look at the concept of “ovarian reserve.” Sometimes a low antral follicle count (AFC) on ultrasound may reflect not only age-related decline, but also the consequence of long-term LH deficiency. In other words, ovarian reserve is not just a static number; it is a dynamic state that is also influenced by its hormonal environment. When the egg continues to grow and reaches the antral stage, its dependence on the combined action of FSH and LH continues.

How is the body’s natural ‘LH surge’ triggered?

The peak of the egg development cycle is the moment when the brain (pituitary gland) suddenly releases a very high amount of LH, known as the “LH surge.” This event triggers the “rupture” of the egg, that is, ovulation. This process is managed by a complex exchange of signals between the brain and the ovaries.

For most of the cycle, estrogen secreted by the ovaries “brakes” hormone production in the brain (negative feedback), keeping the system in balance.

However, when the dominant follicle grows sufficiently and starts producing very high levels of estrogen, this balance changes. When estrogen rises above a certain threshold and stays there for around 50 hours, its effect on the brain reverses: the brake turns into an accelerator (positive feedback).

This positive signal causes the main releasing hormone in the brain (GnRH) to be secreted in a surge-like pattern. This, in turn, gives the pituitary gland the command: “Release all the LH stores now!” The result is the massive LH surge that triggers ovulation.

This sudden surge of LH initiates a series of events inside the egg:

• Completion of the final meiotic division
• Full maturation of the oocyte (MII)
• Expansion of the cumulus cells surrounding the egg
• Weakening of the follicular wall
• Rupture of the follicle (ovulation)

Approximately 34–36 hours after this process begins, the weakened follicle wall ruptures and the mature egg is released.

Why do we need to control LH levels during IVF treatment?

In IVF treatment, our main goals are twofold: First, to ensure that many eggs grow at the same time. Second, to prevent the body from triggering its own LH surge and causing these eggs to “ovulate early” before we are ready to collect them.

If the body produces its own LH surge before we plan it, all the eggs are ovulated uncontrollably and the follicles are empty at the time of egg retrieval (OPU). This means the cycle has to be cancelled. To prevent this “premature ovulation disaster,” we must carefully control the patient’s own LH hormone during treatment. To achieve this control, we use medications called “GnRH analogues.”

Why is the ‘therapeutic window’ of LH level important during treatment?

During IVF treatment, the LH hormone level is considered within a “therapeutic window.” This means we aim for an optimal range in which LH is neither too low nor too high.

If LH levels move outside this window, problems may occur, such as:

• Raw material (androgen) deficiency
• Low estrogen levels
• Arrest in follicular development
• Impaired egg quality
• Excessive pressure on premature egg maturation

Our goal is to keep LH levels within this “ideal range” (approximately 1.2–5.0 IU/L) throughout treatment. This ensures sufficient hormone production for healthy egg growth while preventing levels from rising enough to trigger premature ovulation.

Which protocols are used to prevent an early LH rise (premature surge) during treatment?

In IVF treatment, to prevent “premature ovulation,” it is necessary to suppress the pituitary gland, which controls LH secretion. There are two main protocols (medication approaches) used for this purpose:

GnRH Agonist Protocols (Long Protocol)

In this protocol, “agonist” medications in the form of nasal spray or injections are started in the previous menstrual cycle (around day 21). These drugs initially “flare” the system but, with continuous use, desensitize the receptors in the pituitary and shut down the system completely.

The characteristics of the agonist (long) protocol are:

• Starts in the previous menstrual cycle
• Works by “desensitizing” the pituitary
• Provides deep and stable LH suppression
• The treatment duration is longer
• Usually requires higher medication doses
• Has a higher risk of OHSS (ovarian hyperstimulation syndrome)
• Not suitable for safe triggering with a GnRH agonist

GnRH Antagonist Protocols (Short Protocol)

This is a more modern and “patient-friendly” approach. Ovarian stimulation injections are started on day 2 or 3 of the menstrual cycle. Antagonist injections are added later, when the follicles reach a certain size (usually around stimulation day 6). These drugs act like a “brake.” They bind directly to receptors in the pituitary gland and block them immediately.

The characteristics of the antagonist (short) protocol are:

• Starts at the same time as ovarian stimulation
• Works by “immediately blocking” LH
• Has a shorter treatment duration
• Is a more “patient-friendly” protocol
• Has a significantly lower risk of OHSS
• Allows the option of safe triggering with a GnRH agonist

Today, due to the safety and flexibility it provides, antagonist protocols have become the most widely preferred method around the world.

Why do we monitor LH levels during treatment?

Especially in antagonist (short) protocols, monitoring LH levels with blood tests during treatment allows us to “individualize” therapy. A rising LH level can be a direct signal that it is the right time to start the “brake” mechanism (the antagonist injection).

In addition, after starting the antagonist, LH levels may drop below the “therapeutic window” in some patients. Even if the follicles appear to grow well on ultrasound, an estrogen level lower than expected on blood tests may indicate this “raw material deficiency” (low LH). This may be a sign that we should add medications containing LH from outside.

If we suppress LH, why do we sometimes give LH medication from outside?

This is one of the most delicate balancing points of treatment. Yes, on one hand we suppress LH to prevent premature ovulation. On the other hand, we need a minimal level of LH activity to stay within the therapeutic window. Our goal is not to eliminate LH, but to keep it under control.

In cases of deep suppression created by long agonist protocols, or in patients whose LH drops very low during antagonist protocols, this hormone deficiency becomes a problem. In such situations, we carefully add medications that provide LH activity from outside to bring the level back into the “ideal range.”

The patient groups that most often need external LH support are:

• Patients with hypogonadotropic hypogonadism (HH) (congenital absence of LH/FSH production)
• Older patients
• Patients with low ovarian reserve
• Patients with poor ovarian response in previous treatments
• Patients whose LH level drops excessively during treatment

What is the difference between medications that provide ‘LH activity’?

Medications that provide “LH activity” fall broadly into two categories, and they are not identical to each other; they have important pharmacological differences:

• Recombinant LH (r-LH)

This is a “pure” hormone produced in the laboratory using DNA technology, identical to human LH. Its half-life in the body is short (about 30–60 minutes). When it binds to ovarian cells, it mainly activates signaling pathways related to “growth, survival and protection” of the cell. In other words, it has a more “physiological” and “protective” effect.

• hMG (Human Menopausal Gonadotropin)

hMG is a medication purified from the urine of postmenopausal women and contains both FSH and LH activity. The critical difference is that in modern hMG preparations, the majority of the “LH activity” does not come from natural LH, but from added hCG (the pregnancy hormone). hCG has a very long half-life (24–36 hours). When it binds to the cell, it activates the signaling pathway for “steroidogenesis” (hormone production) much more strongly than LH.

This difference is important, because giving hMG to a patient means delivering a strong and long-acting “hormone production” signal. Giving pure r-LH, on the other hand, means choosing a more physiological, short-acting and “cell-protective” signal.

What is the ‘trigger shot’ and why is it so important?

When the follicles reach the desired size during IVF treatment, a final injection called the “trigger shot” is given approximately 34–36 hours before egg retrieval (OPU).

The purpose of this injection is to mimic the body’s natural “LH surge.” This final signal gives the eggs the command for “final maturation.” Without this signal, even if the eggs are retrieved, they do not have the ability to be fertilized (they remain at the M1 stage). The trigger shot ensures that the egg completes its final meiotic division (reaches MII), achieves nuclear and cytoplasmic maturation, and becomes ready for fertilization. Egg retrieval is performed during the sensitive time window after this injection, when the eggs are fully mature but have not yet been ovulated.

What ‘trigger shot’ options are available for egg maturation?

Today we do not have only one option for egg maturation. Depending on the patient’s condition, especially their OHSS (hyperstimulation) risk, we choose one of three different triggering methods:

Classic hCG Trigger (High-Dose hCG)

This is the oldest and standard method. It has advantages and disadvantages:

• Advantage: Very strong and long-acting
• Advantage: Provides strong luteal support for fresh transfer
• Disadvantage: Carries a high risk of OHSS
• Disadvantage: Can be dangerous in high-response patients

Safe Trigger (GnRH Agonist)

This is a modern and safe method that can only be used in antagonist protocols. Instead of giving hCG, a GnRH agonist injection is used to trigger the patient’s own LH and FSH surge.

• Advantage: Induces the body’s own natural LH and FSH surge
• Advantage: Eliminates the risk of OHSS
• Advantage: Often results in more mature (MII) oocytes
• Disadvantage: Severely weakens luteal support
• Disadvantage: Does not allow fresh embryo transfer
• Requirement: Requires freezing of all embryos (freeze-all)

Dual Trigger (GnRH-a + Low-Dose hCG)

This is the most up-to-date approach designed to combine the advantages of both methods. The patient receives both a GnRH agonist to induce their own surge and a very low dose of hCG to support the uterus.

• Advantage: Provides high oocyte maturation with a natural-like LH/FSH surge
• Advantage: Provides adequate luteal support for fresh transfer with low-dose hCG
• Advantage: Keeps OHSS risk to a minimum
• Advantage: Increases safety while preserving the chance of fresh transfer
• Ideal Use: Normal/high responders
• Ideal Use: Patients with previous problems of oocyte maturation

How is the most suitable protocol for me chosen among all these LH options?

In IVF treatment, there is no “one-size-fits-all” protocol. The key to success is to personalize treatment by combining physiological principles with the most up-to-date evidence. A strategy is determined according to the patient’s age, ovarian reserve, response in previous treatments and, most importantly, the risk of OHSS.

In patients with high ovarian reserve (for example, those with Polycystic Ovary Syndrome), safety is the first priority. In these patients, it is essential to reduce the risk of OHSS to zero. Therefore, the antagonist (short) protocol is preferred. For triggering, the “Safe Trigger” (GnRH agonist) is used and all embryos are frozen (freeze-all). In this group, external LH support is usually not necessary.

In patients with low ovarian reserve or advanced age, the goal is to obtain maximum quality from the few available eggs. In this group, adding LH-containing medications (hMG or r-LH) to the treatment may improve oocyte quality and embryo development.

Patients with normal ovarian response are the most flexible group. In them, the antagonist protocol is usually preferred because it is “patient-friendly” and offers safety flexibility. As the trigger shot, “Dual Trigger” is often the best balance, as it preserves the chance of fresh embryo transfer while minimizing OHSS risk.

Frequently Asked Questions